We propose to develop an in vivo assay that will test for diffusible trophic agents that operate in the central nervous system. Our long term objective is to use these agents to effect behavioral recovery after CNS injury. The particular experiments outlined in this proposal are based on our previous work using CNS transplantation and tissue culture methods. These studies suggest that there are highly specific trophic interactions in the developing visual system of the rat, and led us to design the present tests for specific diffusible trophic agents. We propose to develop a system for sustained release of conditioned culture medium into the brain of the neonatal rat. The medium will be obtained from cultures of neocortical cells -- cells that are able to prolong the survival of dorsal lateral geniculate neurons when they are transplanted into the brain of a newborn rat with its entire posterior cortex removed. Preliminary tests indicate that two gel delivery systems, polyacrylamide chips and alginate beads, may be suitable for supplying the culture medium over an appropriate time course. We propose to test these delivery systems in order to find the optimal concentrations of the gels for sustained release of proteins with a variety of molecular weights. The beads or chips containing the conditioned culture medium will then be implanted into the cavity of the cortical lesion to test the idea that diffusible cortical cell products are responsible for protecting the geniculate neurons from degeneration. These experiments represent important tests of the 'trophic hypothesis' in the central nervous system and may lead to the identification of agents that promote repair after CNS injury.